Trial Outcomes & Findings for Effect of Citrate Dialysate on Vascular Calcification (NCT NCT04956120)

NCT ID: NCT04956120

Last Updated: 2026-05-05

Results Overview

Rate of progression of breast arterial calcification (BAC) is calculated by linear regression of 3 mammograms over one year in each treatment arm (Months 0, 6 and 12 versus Months 12, 18 and 24). Progression of calcification is quantified as the length of calcified artery segments per year, measured in millimeters. Slower progression of vascular calcification, indicated by lower values, is a desirable outcome.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

54 participants

Primary outcome timeframe

3 measurements during 12 months of treatment for each study period (up to 24 months for both years of the study)

Results posted on

2026-05-05

Participant Flow

The first individual gave informed consent to participate on May 27, 2021 and all study follow up was complete by March 18, 2025. Participants were enrolled from Emory Dialysis centers in Atlanta and Decatur, Georgia, USA.

Participant milestones

Participant milestones
Measure
Citrate Dialysate Then Standard Dialysate
Participants receiving hemodialysis using a citrate acid concentrate dialysate for the first year of the study, then receiving hemodialysis using a non-citrate acid concentrate dialysate (standard dialysate) for the second year of the study. Citrate Dialysate: Dialysate is generated during dialysate from two concentrates (acid concentrate and bicarbonate concentrate) mixed with treated water. When used, citrate is provided in the acid concentrate. The acid concentrate with citrate is approved for this use by the FDA and will be used according to standard procedures without altered dialysis machine settings. Standard Dialysate: Dialysate is generated during dialysate from two concentrates (acid concentrate and bicarbonate concentrate) mixed with treated water. The acid concentrate without citrate is approved for this use by the FDA and will be used according to standard procedures without altered dialysis machine settings.
Standard Dialysate Then Citrate Dialysate
Participants receiving hemodialysis using a non-citrate acid concentrate dialysate for the first year of the study, then receiving hemodialysis using a citrate acid concentrate dialysate for the second year of the study. Citrate Dialysate: Dialysate is generated during dialysate from two concentrates (acid concentrate and bicarbonate concentrate) mixed with treated water. When used, citrate is provided in the acid concentrate. The acid concentrate with citrate is approved for this use by the FDA and will be used according to standard procedures without altered dialysis machine settings. Standard Dialysate: Dialysate is generated during dialysate from two concentrates (acid concentrate and bicarbonate concentrate) mixed with treated water. The acid concentrate without citrate is approved for this use by the FDA and will be used according to standard procedures without altered dialysis machine settings.
First year of study
STARTED
29
25
First year of study
COMPLETED
17
17
First year of study
NOT COMPLETED
12
8
Second year of study
STARTED
17
17
Second year of study
COMPLETED
16
13
Second year of study
NOT COMPLETED
1
4

Reasons for withdrawal

Reasons for withdrawal
Measure
Citrate Dialysate Then Standard Dialysate
Participants receiving hemodialysis using a citrate acid concentrate dialysate for the first year of the study, then receiving hemodialysis using a non-citrate acid concentrate dialysate (standard dialysate) for the second year of the study. Citrate Dialysate: Dialysate is generated during dialysate from two concentrates (acid concentrate and bicarbonate concentrate) mixed with treated water. When used, citrate is provided in the acid concentrate. The acid concentrate with citrate is approved for this use by the FDA and will be used according to standard procedures without altered dialysis machine settings. Standard Dialysate: Dialysate is generated during dialysate from two concentrates (acid concentrate and bicarbonate concentrate) mixed with treated water. The acid concentrate without citrate is approved for this use by the FDA and will be used according to standard procedures without altered dialysis machine settings.
Standard Dialysate Then Citrate Dialysate
Participants receiving hemodialysis using a non-citrate acid concentrate dialysate for the first year of the study, then receiving hemodialysis using a citrate acid concentrate dialysate for the second year of the study. Citrate Dialysate: Dialysate is generated during dialysate from two concentrates (acid concentrate and bicarbonate concentrate) mixed with treated water. When used, citrate is provided in the acid concentrate. The acid concentrate with citrate is approved for this use by the FDA and will be used according to standard procedures without altered dialysis machine settings. Standard Dialysate: Dialysate is generated during dialysate from two concentrates (acid concentrate and bicarbonate concentrate) mixed with treated water. The acid concentrate without citrate is approved for this use by the FDA and will be used according to standard procedures without altered dialysis machine settings.
First year of study
Death
2
4
First year of study
Lost to Follow-up
5
2
First year of study
Physician Decision
3
1
First year of study
Protocol Violation
1
0
First year of study
Withdrawal by Subject
1
1
Second year of study
Death
1
1
Second year of study
Lost to Follow-up
0
2
Second year of study
Withdrawal by Subject
0
1

Baseline Characteristics

Effect of Citrate Dialysate on Vascular Calcification

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Citrate Dialysate Then Standard Dialysate
n=29 Participants
Participants receiving hemodialysis using a citrate acid concentrate dialysate for the first year of the study, then receiving hemodialysis using a non-citrate acid concentrate dialysate (standard dialysate) for the second year of the study.
Standard Dialysate Then Citrate Dialysate
n=25 Participants
Participants receiving hemodialysis using a non-citrate acid concentrate dialysate for the first year of the study, then receiving hemodialysis using a citrate acid concentrate dialysate for the second year of the study.
Total
n=54 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=54 Participants
0 Participants
n=60 Participants
0 Participants
n=114 Participants
Age, Categorical
Between 18 and 65 years
22 Participants
n=54 Participants
18 Participants
n=60 Participants
40 Participants
n=114 Participants
Age, Categorical
>=65 years
7 Participants
n=54 Participants
7 Participants
n=60 Participants
14 Participants
n=114 Participants
Age, Continuous
56.4 years
STANDARD_DEVIATION 9.5 • n=54 Participants
59.8 years
STANDARD_DEVIATION 11.3 • n=60 Participants
58.0 years
STANDARD_DEVIATION 10.4 • n=114 Participants
Sex: Female, Male
Female
29 Participants
n=54 Participants
25 Participants
n=60 Participants
54 Participants
n=114 Participants
Sex: Female, Male
Male
0 Participants
n=54 Participants
0 Participants
n=60 Participants
0 Participants
n=114 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants
n=54 Participants
0 Participants
n=60 Participants
0 Participants
n=114 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
29 Participants
n=54 Participants
25 Participants
n=60 Participants
54 Participants
n=114 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=54 Participants
0 Participants
n=60 Participants
0 Participants
n=114 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=54 Participants
0 Participants
n=60 Participants
0 Participants
n=114 Participants
Race (NIH/OMB)
Asian
0 Participants
n=54 Participants
0 Participants
n=60 Participants
0 Participants
n=114 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=54 Participants
0 Participants
n=60 Participants
0 Participants
n=114 Participants
Race (NIH/OMB)
Black or African American
29 Participants
n=54 Participants
25 Participants
n=60 Participants
54 Participants
n=114 Participants
Race (NIH/OMB)
White
0 Participants
n=54 Participants
0 Participants
n=60 Participants
0 Participants
n=114 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=54 Participants
0 Participants
n=60 Participants
0 Participants
n=114 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=54 Participants
0 Participants
n=60 Participants
0 Participants
n=114 Participants
Region of Enrollment
United States
29 Participants
n=54 Participants
25 Participants
n=60 Participants
54 Participants
n=114 Participants

PRIMARY outcome

Timeframe: 3 measurements during 12 months of treatment for each study period (up to 24 months for both years of the study)

Population: This analysis includes participants who completed both years of the study. One participant was excluded from due to the mammograms having inconsistent breast coverage resulting in the scans not being adequate for measurement of breast arterial calcification (BAC), providing a sample size of 28 participants for analysis.

Rate of progression of breast arterial calcification (BAC) is calculated by linear regression of 3 mammograms over one year in each treatment arm (Months 0, 6 and 12 versus Months 12, 18 and 24). Progression of calcification is quantified as the length of calcified artery segments per year, measured in millimeters. Slower progression of vascular calcification, indicated by lower values, is a desirable outcome.

Outcome measures

Outcome measures
Measure
Citrate Dialysate
n=28 Participants
Participants receiving hemodialysis using a citrate acid concentrate dialysate during the first year of the study, or the second year of the study.
Standard Dialysate
n=28 Participants
Participants receiving hemodialysis using a non-citrate acid concentrate dialysate for the first year of the study, or the second year of the study.
Length of Calcified Artery Segments
47 millimeters (mm) per year
Interval 10.0 to 124.0
9 millimeters (mm) per year
Interval -4.0 to 34.0

SECONDARY outcome

Timeframe: Pre-HD and Post-HD during each study period (up to 24 months for both years of the study)

Population: This analysis includes participants completing both years of the study. One participant was excluded from due to the mammograms having inconsistent breast coverage resulting in the scans not being adequate for measurement of BAC, providing a sample size of 28 participants for analysis. Post-dialysis serum iCa was not measured in one participant during the citrate arm. During the standard dialysate arm, pre-dialysis serum iCa was missing on one participant, post-dialysis iCa on two participants.

Blood samples were drawn to assess mineral metabolism prior to hemodialysis (HD) and after HD. The values are the mean milligrams (mg) of ionized calcium per deciliter (dL) of blood from two measurements during each study period.

Outcome measures

Outcome measures
Measure
Citrate Dialysate
n=28 Participants
Participants receiving hemodialysis using a citrate acid concentrate dialysate during the first year of the study, or the second year of the study.
Standard Dialysate
n=27 Participants
Participants receiving hemodialysis using a non-citrate acid concentrate dialysate for the first year of the study, or the second year of the study.
Serum Ionized Calcium (iCa)
Pre-HD
4.8 mg/dL
Standard Error 0.07
4.8 mg/dL
Standard Error 0.10
Serum Ionized Calcium (iCa)
Post-HD
4.6 mg/dL
Standard Error 0.04
4.9 mg/dL
Standard Error 0.08

SECONDARY outcome

Timeframe: Pre-HD and Post-HD during each study period (up to 24 months for both years of the study)

Population: This analysis includes participants completing both years of the study. One participant was excluded from due to the mammograms having inconsistent breast coverage resulting in the scans not being adequate for measurement of BAC, providing a sample size of 28 participants for analysis. Both pre-dialysis and post-dialysis serum Mg are missing for two participants during the standard dialysate arm.

Blood samples were drawn to assess mineral metabolism prior to and after hemodialysis (HD). The values are mean milligrams (mg) of magnesium per deciliter (dL) of blood from two measurements during each study period.

Outcome measures

Outcome measures
Measure
Citrate Dialysate
n=28 Participants
Participants receiving hemodialysis using a citrate acid concentrate dialysate during the first year of the study, or the second year of the study.
Standard Dialysate
n=26 Participants
Participants receiving hemodialysis using a non-citrate acid concentrate dialysate for the first year of the study, or the second year of the study.
Serum Magnesium (Mg)
Post-HD
2.0 mg/dL
Standard Error 0.02
2.1 mg/dL
Standard Error 0.03
Serum Magnesium (Mg)
Pre-HD
2.3 mg/dL
Standard Error 0.04
2.4 mg/dL
Standard Error 0.07

SECONDARY outcome

Timeframe: Pre-HD and Post-HD during each study period (up to 24 months for both years of the study)

Population: This analysis includes participants completing both years of the study. One participant was excluded from due to the mammograms having inconsistent breast coverage resulting in the scans not being adequate for measurement of BAC, providing a sample size of 28 participants for analysis. Plasma citrate was not measured in 3 participants who were at the furthest outlying dialysis center, due to logistical issues.

Blood samples were drawn to assess mineral metabolism prior to hemodialysis (HD) and after HD. The values are the mean from two measurements during each study period.

Outcome measures

Outcome measures
Measure
Citrate Dialysate
n=25 Participants
Participants receiving hemodialysis using a citrate acid concentrate dialysate during the first year of the study, or the second year of the study.
Standard Dialysate
n=25 Participants
Participants receiving hemodialysis using a non-citrate acid concentrate dialysate for the first year of the study, or the second year of the study.
Plasma Citrate
Pre-HD
134 micrometer (uM)
Standard Error 9
130 micrometer (uM)
Standard Error 7
Plasma Citrate
Post-HD
383 micrometer (uM)
Standard Error 16
187 micrometer (uM)
Standard Error 20

Adverse Events

Citrate Dialysate

Serious events: 0 serious events
Other events: 0 other events
Deaths: 3 deaths

Standard Dialysate

Serious events: 0 serious events
Other events: 0 other events
Deaths: 5 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

W. Charles O'Neill, MD

Emory University

Phone: 404-727-3922

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place